Critical to our understanding of the pathophysiology of Sudden Infant Death Syndrome is a detailed description of how the neurons that control respiration normally develop. To date, there is little information available concerning the normal physiological and anatomical development of any mammalian neuron including those controlling respiration. This proposal presents studies that will explore the cellular mechanisms underlying the normal development of two mammalian respiratory motoneurons, the genioglossal motoneurons innervating the posterior tongue and the phrenic motoneurons innervating the diaphragm. The coordinated activity of these two muscles are very important to generation of a breath in that the genioglossus muscle must open the airways prior to the diaphragm generating an inspiratory effort. Dyscoordination between these muscles is believed to result in the obstructive apnea, characteristic of SIDS. We have found a period during normal postnatal development when these respiratory motoneurons are harder to excite. During this period, the brain must generate more effort to activate these neurons and thereby, increasing the likelihood of some kind of muscle failure leading to inadequate ventilation. It is conceivable, in some instances, that a simple complications like a mild viral infection during this period may precipitate the unanticipated death of an otherwise healthy appearing infant. Two hypotheses will test whether synaptic input and/or voltage- dependent potassium channels are responsible for this period of hypoexcitability. The electrophysiology and morphology of individual genioglossal and phrenic motoneurons will be examined using intracellular recording and labeling in slice preparations of the rat brainstem and spinal cord. The contribution of various inhibitory and excitatory neurotransmitters will be valuated using a variety of pharmacological blockers. The postnatal variation in the distribution and density of inhibitory synapses on phrenic and genioglossal motoneurons will be described using antibodies to glutamic acid decarboxylase (GABAergic synapse) and to the postsynaptic glycine receptor. Then, the contribution of potassium channels located on the motoneuron will be assessed by blocking one specific channel by intracellular injection of cesium. This change in the properties of these motoneurons is proposed to represent an important stage in the differentiation of these cells into their adult form.